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Biomedical subjects

A Belfiore

Publications and source records attributed to A Belfiore.

At least 19 recordsLinked to original sources
PubMed2006

Growth hormone status in morbidly obese subjects and correlation with body composition.

Morbidly obese subjects are characterized by multiple endocrine abnormalities and these are paralleled by unfavorable changes in body composition. In obese individuals, either 24-h spontaneous or stimulated GH secretion is impaired without an organic pituitary disease and the severity of the secretory defect is proportional to the degree of obesity. The GHRH+arginine (GHRH+ARG) test is likely to be the overall test of choice in clinical practice to differentiate GH deficiency (GHD) patients. Similarly to other provocative tests, GHRH+ARG is influenced by obesity per se. Therefore, a new cut-off limit of peak GH response of 4.2 microg/l in obese subjects has been recently assumed. The aim of the present study was to investigate the reciprocal influence between decreased GH secretion and body composition in a group of 110 morbidly obese subjects, using the new cut-off limit of peak GH response to GHRH+ARG test for these subjects. In our study, GHD was identified in 27.3% of the obese subjects, without gender difference. In GDH obese subjects body mass index (BMI), waist circumference, waist-to-hip ratio (WHR), fat mass (FM), and resistance (R) were higher while reactance (Xc), phase angle, body cell mass (BCM), IGF-I, or IGF-I z-scores were lower than in normal responders (p<0.001). In all obese subjects, GH peak levels showed a negative correlation with age, BMI, waist circumference and FM, and a positive correlation with IGF-I. In the stepwise multiple linear regression, waist circumference and FM were the major determinants of GH peak levels and IGF-I. In conclusion, using the new cut-off limit of peak GH response to GHRH+ARG test for obese subjects, about 1/3 morbidly obese subjects were GHD. GHD subjects showed a significantly different body composition compared with normal responders, and the secretory defect was correlated to different anthropometric variables with waist circumference and FM as the major determinants.

Adipose Tissue↗
PubMed2005

Role of dehydroepiandrosterone sulfate levels on body composition after laparoscopic adjustable gastric banding in pre-menopausal morbidly obese women.

UNLABELLED: In humans, dehydroepiandrosterone (DHEAS) has been postulated to have anabolic and lipolytic properties that could potentially counteract the catabolic effect of cortisol. DHEAS secretion is reduced in morbid obesity, likely due to hyperinsulinemia, and laparoscopic adjustable gastric banding (LASGB), by inducing considerable and rapid weight loss, reduces insulin levels. To investigate the role of decreased insulin levels after LASGB-induced weight loss on DHEAS levels and on body composition changes, we studied 30 pre-menopausal morbidly obese women (BMI ranging 37-62 kg/m2) before, 6, 12 and 24 months after LASGB. Total body water (TBW), fat-free mass (FFM) and fat mass (FM) were measured by bioelectrical impedance analysis; tissue hydration was also assessed by impedance vector analysis. At study ending, the subjects had a total weight loss of 28% of baseline body weight (15% after 6 months). After LASGB, weight loss was mainly due to decreased FM, and TBW, FFM, and body hydration were not significantly reduced. Weight loss was associated with an 82% rise in serum DHEAS already after 6 months while cortisol, cortisol/DHEAS molar ratio, and insulin levels fell by 5.5, 62 and 50%, respectively, after 6, 12 and 24 months (p<0.05). CONCLUSIONS: LASGB associated with a well balanced low-calorie diet permits a satisfactory 2-yr weight loss, sparing FFM and without body fluid alterations. As the result of a stable weight reduction program weight loss is associated to decrease in cortisol, cortisol/DHEAS molar ratio, and insulin plasma levels with marked rise in DHEAS. Higher cortisol/DHEAS molar ratio values at baseline are also associated to lower weight loss after LASGB, with lower decrease in FM and higher reduction in FFM and body cell mass, in spite of no differences in dietary regimes. Cortisol/DHEAS molar ratio is likely to represent a reliable marker of favourable modifications in body composition.

Adult↗
PubMed2004

Isolated monolateral neurosensory hearing loss as a rare sign of neuroborreliosis.

Lyme disease, or borreliosis, is a zoonosis transmitted by Borrelia burgdorferi which also involves the central nervous system (CNS), in 15% of affected individuals, with the occurrence of aseptic meningitis, fluctuating meningoencephalitis, or neuropathy of cranial and peripheral nerves. Encephalopathy with white matter lesions revealed by magnetic resonance imaging (MRI) scans in late, persistent stages of Lyme disease has been described. In this report, we describe a patient with few clinical manifestations involving exclusively the eighth cranial nerve, monolaterally and diffuse bilateral alterations of the white matter, particularly in the subcortical periventricular regions at cerebral MRI. This single patient study shows that the search for antibodies against Borrelia burgdoferi should always be performed when we face a leukoencephalopathy of unknown origin. An isolated lesion of the eighth cranial nerve can be the only neurologic sign in patients with leukoencephalopathy complicating Lyme disease.

Adult↗
PubMed2003

Early carotid atherosclerosis in normotensive severe obese premenopausal women with low DHEA(S).

The aim of this study was to investigate the direct involvement of hyperinsulinaemia, DHEA and DHEA-S [DHEA(S)] in severe obesity in early carotid atherosclerosis, measured as intima-media thickness (IMT). Seventeen normotensive premenopausal women with very high BMI (43.5 +/- 1.6 kg/m2) were recruited for the study. Six women were also evaluated 12 months after laparoscopic adjustable silicone gastric banding (LASGB). Dietary intake, fasting plasma lipid profile, glycemic and insulinemic response to the OGTT, adrenal secretion, at baseline and after ACTH stimulation test, were measured. IMT, common carotid diameter (CD) and left ventricular mass index (LVMi) were measured by B-mode echotomography. All obese subjects showed higher fasting and stimulated insulin levels, but lower DHEA(S) levels than controls, showing a negative correlation between both fasting and stimulated insulin and DHEA(S), either at baseline or after ACTH testing. IMT was higher (p < 0.05) than controls, with a positive correlation with stimulated insulin (p < 0.05) and a strong negative correlation with DHEA(S) (p < 0.001). In a multiple linear regression analysis, insulin response to OGTT maintained an association with DHEA(S) independent of fasting insulin, while DHEA maintained the association with IMT independent of stimulated insulin (p < 0.0001). In the six patients evaluated 12 months after LASGB, fasting insulin levels decreased, while DHEA(S) levels increased (p < 0.05). In conclusion, an early cardiovascular involvement was detected in this group of severe obese with hyperinsulinaemia and low DHEA(S), even in the absence of other well known CVD risk factors.

Adult↗
PubMed2002

Differentiated thyroid cancer in children and adolescents.

In this retrospective study we analyzed cancer characteristics and outcome in a consecutive series of 48 young patients (< or =20 yr of age) with a differentiated thyroid cancer (DTC), observed during the period 1977-1998. In none of them was thyroid cancer related to ionizing radiation. The median age was 18.1 yr, range 7-20, and the female/male ratio was 2.5/1. Papillary thyroid cancer (PTC) occurred in 83% and follicular thyroid cancer (FTC) in 17% of cases. All patients underwent total or near total thyroidectomy plus pre- and/or paratracheal lymphnode dissection. Surgery complication rate was low (4% permanent hypoparathyroidism; no permanent lesion of recurrent laryngeal nerve). Extrathyroid disease was present in 52% of patients with PTC and in 50% of patients with FTC, while nodal metastases were present in 62.5% of patients with PTC and in 12.5% of patients with FTC. Lung metastases occurred in 10 patients with PTC (25%) and in none with FTC. Twenty-one patients required radioiodine treatment for metastatic disease: 11 patients for relapsing lymph-node metastases, 4 patients for lung metastases, 6 patients for both lymph-node and lung metastases. After a mean follow-up of 85+/-12 months all patients followed regularly (no.=47) were alive; 37 patients (79%) were free of disease and 10 (21%) had residual disease. Our results indicate that non-radiation-related DTC occurring in young patients often presents at an advanced stage. For this reason, although the prognosis is usually good in these patients, we believe that total or near total thyroidectomy with lymphadenectomy is always the required initial surgical treatment.

Adenocarcinoma, Follicular↗
PubMed2001

Fine-needle aspiration biopsy of the thyroid.

The routine use of thyroid FNAB caused profound changes in the management of thyroid nodules. FNAB allows a prompt identification and treatment of thyroid malignancies and avoids unnecessary surgery in patients with benign lesions, improving quality of life in patients with thyroid nodules. Furthermore, FNAB provides guidance for the type of surgery and reduces costs of care. On average, standard FNAB is nondiagnostic in 25% to 40% of cases, which include inadequate specimens and indeterminate (suspicious) diagnoses. In addition, a small percentage of false-negative diagnoses occur, which are unavoidable and raise concern of a late diagnosis of cancer. To minimize the limitations of FNAB, every center should reach and maintain a high standard of expertise in all of the steps of smear preparation and interpretation. Alternative modes of sampling or sample preparation may result in a reduction of nondiagnostic samples and better accuracy. Every center should set up clinical guidelines tailored to their own FNAB results and including the evaluation of clinical data. More work is needed to increase the accuracy of FNAB in suspicious cases. Toward this goal a variety of molecular markers have been evaluated; although none of them are ideal, some are promising. More studies need to be carried out in larger series to further evaluate the accuracy of these markers in identifying specific cancer histotypes within the group of suspicious lesions. It is hoped that, in the near future, the routine use of a combination of these markers will cost-effectively improve the diagnosis of malignant nodules classified as suspicious on traditional cytology. Statistical methods such as bayesian analysis or neural networks can be advantageously used to integrate different relevant information derived from family and personal history, clinical data, cytologic results, and evaluation of molecular markers.

Biopsy, Needle↗
PubMed2001

Immunostaining for Met/HGF receptor may be useful to identify malignancies in thyroid lesions classified suspicious at fine-needle aspiration biopsy.

The receptor for hepatocyte growth factor (Met) is not expressed in the normal thyroid but it is overexpressed in most thyroid carcinomas. We evaluated whether Met immunostaining of cytological smears from fine-needle aspiration biopsy (FNAB) may be useful for the preoperative diagnosis of thyroid cancer. Notably, routine cytological examination often fails to distinguish well-differentiated follicular carcinomas and a proportion of papillary carcinomas (low-grade papillary carcinomas and papillary carcinomas follicular variant [FVPTC]) from benign lesions: all these lesions are usually classified as suspicious. We examined 80 thyroid lesions diagnosed as suspicious at cytology that had subsequently undergone surgery. The histologic diagnosis had been: papillary carcinomas (n = 14), FVPTC (n = 11), follicular carcinomas (n = 25), atypical follicular adenomas (n = 5), follicular adenomas (n = 20), and nodular goiters (n = 5). We also studied typical papillary carcinomas (n = 30) and nodular goiters (n = 10), all correctly diagnosed at cytology. In lesions classified suspicious at routine cytology, Met immunostaining was positive in 12 of 14 (85.7%) papillary carcinomas, 8 of 11 (72.7%) FVPTC, 7 of 25 (28%) follicular carcinomas, and 5 of 5 atypical adenomas. In contrast, none of the 25 lesions cytologically suspicious but benign at histology were positive. These data suggest that Met immunostaining of suspicious cytological smears are useful for identifying malignant lesions, especially those with a papillary histotype.

Adenocarcinoma, Follicular↗
PubMed2001

The IGF system in thyroid cancer: new concepts.

In recent years, the activation of the insulin-like growth factor (IGF) system in cancer has emerged as a key factor for tumour progression and resistance to apoptosis. Therefore, a variety of strategies have been developed to block the type I IGF receptor (IGF-I-R), which is thought to mediate the biological effects of both IGF-I and IGF-II. However, recent data suggest that the IGF signalling system is complex and that other receptors are involved. To unravel the complexity of the IGF system in thyroid cancer, IGF-I and IGF-II production, and the expression and function of their cognate receptors were studied. Both IGFs were found to be locally produced in thyroid cancer: IGF-I by stromal cells and IGF-II by malignant thyrocytes. Values were significantly higher in malignant tissue than in normal tissue. IGF-I-Rs were overexpressed in differentiated papillary carcinomas but not in poorly differentiated or undifferentiated tumours, whereas insulin receptors (IRs) were greatly overexpressed in all tumour hystotypes, with a trend for higher values in dedifferentiated tumours. As a consequence of IR overexpression, high amounts of IR/IGF-I-R hybrids (which bind IGF-I with high affinity) were present in all thyroid cancer histotypes. Because of recent evidence that isoform A of IR (IR-A) is a physiological receptor for IGF-II in fetal life, the relative abundance of IR-A in thyroid cancer was measured. Preliminary data indicate that overexpressed IRs mainly occur as IR-A in thyroid cancer. These data indicate that both IR/IGF-I-R hybrids and IR-A play an important role in the overactivation of the IGF system in thyroid cancer and in IGF-I mitogenic signalling in these tumours. J Clin PATHOL: Mol Pathol

Carcinoma, Papillary↗
PubMed2000

Appearance of antithyroglobulin antibodies as the sole sign of metastatic lymph nodes in a patient operated on for papillary thyroid cancer: a case report.

We report a case in which the appearance of a progressively rising titer of thyroglobulin (Tg) antibodies was the most sensitive marker of papillary thyroid cancer relapse at loco-regional lymph nodes. The patient, a 60-year-old man, had been treated with total thyroidectomy plus lymphadenectomy and radioiodine ablation for a 1-cm papillary thyroid cancer. Twelve years after surgery, while undergoing levothyroxine (LT4) therapy, Tg antibodies were first detected and progressively rose from 99 to 1,697 U/mL in 18 months, while serum Tg remained undetectable. Both neck ultrasonography and 131I whole-body scan (WBS) were unremarkable. Enlarged lymph nodes became palpable at the left laterocervical region only 2 years after the first appearance of Tg antibodies and were surgically removed after cancer relapse was confirmed by fine-needle aspiration cytology. This case emphasizes the possibility that in thyroid cancer patients who have undergone total thyroidectomy, the appearance of Tg antibodies may indicate metastatic lymph nodes even when serum Tg is undetectable and WBS negative.

Antibodies↗
PubMed2000

[Differentiated carcinoma of the thyroid in the young. Clinical and histopathologic aspects].

BACKGROUND: The surgical approach to Differentiated Thyroid Carcinoma (DTC) is controversial. Aim of this study is to evaluate the opportunity of total thyroidectomy as treatment of choice for DTC in children. METHODS: We examined the tumor features at diagnosis, the complications of surgery and the clinical outcome in a consecutive series of 33 young patients, (age range 7-19 yrs), who underwent total thyroidectomy for DTC as compared to a consecutive series of 181 adult patients operated for DTC (age range 20-64 yrs). RESULTS: Histopathological examination has shown that bilateral foci of the tumor and extrathyroidal extension, were present with similar frequency in both groups of patients (15 vs 18% and 39 vs 48% respectively); node metastases and distant metastases were more frequent in young patients than in adult patients. Complications of total thyroidectomy were not frequent with 6% of permanent hypoparathyroidism. No case of laryngeal nerve damage was observed. In 7/8 patients with lung metastases the radioiodine treatment was effective: in four patients we observed a complete remission of disease, and in three patients a partial response with a decrease of Tg levels and a reduction of the radioiodine uptake areas. CONCLUSIONS: Thyroid carcinoma is not less aggressive in children than in adults. Total thyroidectomy plus lymph node dissections appears to be the treatment of choice as routine surgical treatment of DTC in children. Radioiodine therapy gives good results for the treatment of lung metastases.

Adolescent↗
PubMed1999

Insulin receptor activation by IGF-II in breast cancers: evidence for a new autocrine/paracrine mechanism.

IGF-II, produced by breast cancer epithelial and stromal cells, enhances tumor growth by activating the IGF-I receptor (IGF-I-R) via autocrine and paracrine mechanisms. Previously we found that the insulin receptor (IR), which is related to the IGF-I-R, is overexpressed in breast cancer cells. Herein, we find that, in breast cancer the IR is activated by IGF-II. In eight human breast cancer cell lines studied there was high affinity IGF-II binding to the IR, with subsequent IR activation. In these lines, IGF-II had a potency up to 63% that of insulin. In contrast, in non malignant human breast cells, IGF-II was less than 1% potent as insulin. Via activation of the IR tyrosine kinase IGF-II stimulated breast cancer cell growth. Moreover, IGF-II also activated the IR in breast cancer tissue specimens; IGF-II was 10-100% as potent as insulin. The IR occurs in two isoforms generated by alternative splicing of exon 11; these isoforms are IR-A (Ex11-) and IR-B (Ex11+). IR-A was predominantly expressed in breast cancer cells and specimens and the potency of IGF-II was correlated to the expression of this isoform (P<0.0001). These data indicate, therefore, that the IR-A, which binds IGF-II with high affinity, is predominantly expressed in breast cancer cells and represents a new autocrine/paracrine loop involved in tumor biology.

Binding, Competitive↗
PubMed1999

Expression of neurotrophins, GDNF, and their receptors in rat thyroid tissue.

Levels of mRNA for neurotrophins (brain-derived neurotrophic factor, BDNF; neurotrophin 3, NT-3; neurotrophin 4, NT-4) and their receptors (trkA, trkB, trkC) and for glial cell line-derived neurotrophic factor (GDNF) and its receptors (ret, GDNFR-alpha) were measured in rat thyroid tissue by ribonuclease protection assays. In thyroid tissue the NT-3 mRNA level was threefold lower and the NT-4 mRNA level sixfold higher than those detected in adult rat hippocampus, while BDNF mRNA was undetectable. Very low levels of mRNA for truncated trkB and trkC receptors and no catalytic trkA, trkB or trkC were found. In conclusion NT-3 and NT-4, but not the corresponding functional receptors, are expressed in the thyroid tissue. Therefore, it is unlikely that these factors serve a direct local autocrine or paracrine function in thyroid cell types, and a target-derived mode of action on neurons innervating the thyroid tissue is suggested. An opposite result has been found for the neurotrophic factor GDNF: thyroid tissue showed a high level of transcripts for the GDNF receptor subunits (GDNFR-alpha and Ret), while GDNF mRNA was undetectable. The in situ hybridization analysis of GDNFR-alpha and ret mRNA revealed an interesting difference in the cell distribution of these transcripts: ret mRNA is selectively expressed in a subpopulation of cells scattered in the follicular epithelium and in the interfollicular spaces, while GDNFR-alpha expression is more homogeneous and widespread, including the more abundant cell type of the thyroid gland: the follicular cell. Double-labeling in situ hybridization/immunocytochemistry experiments, with a specific marker (calcitonin), showed that parafollicular cells express ret but not GDNFR-alpha. This differential distribution of the GDNF receptor components (GDNFR-alpha and ret) may reflect a peculiar biological role in intercellular communication in the thyroid gland.

Animals↗
PubMed1999

Insulin/IGF-I hybrid receptors play a major role in IGF-I signaling in thyroid cancer.

The insulin-like growth factor-I (IGF-I) plays an important role in determining the biological behavior of a variety of malignancies. We measured IGF-I, its receptor and related receptors in thyroid cancer. IGF-I was present both in normal thyroid tissue and in thyroid cancer tissue and it was produced by stromal cells but not by thyrocytes. Values were significantly higher in malignant than in normal tissue. IGF-I receptors (IGF-I-Rs) and the homologous insulin receptors (IRs) were found overexpressed in both thyroid cancer cell lines (n = 4) and specimens (n = 17) as compared to normal values. In addition, high levels of hybrid IGF-I/insulin receptors (IR/IGF-I-Rs) were present in both thyroid cancer specimens and cell lines. IR/IGF-I-R hybrids were the most represented type of receptor in 14/17 specimens and exceeded the IGF-I-R content in all cases. Hybrid content correlated with the IR and IGF-I-R content, suggesting that in thyroid tissue hybrid formation occurs by random assembly of IR and IGF-I-R half receptors. Hybrid receptor autophosphorylation was stimulated by IGF-I with high affinity. In cells with a high IR/IGF-I-Rs content, blocking antibodies specific to these receptors substantially inhibited IGF-I induced cell growth. These data indicate that the IGF-I system is overactivated in thyroid cancer and that IR/IGF-I-R hybrid receptors play an important role in IGF-I mitogenic signaling in these tumors.

Cell Line↗
PubMed1999

Insulin receptor isoform A, a newly recognized, high-affinity insulin-like growth factor II receptor in fetal and cancer cells.

Insulin-like growth factor II (IGF-II) is a peptide growth factor that is homologous to both insulin-like growth factor I (IGF-I) and insulin and plays an important role in embryonic development and carcinogenesis. IGF-II is believed to mediate its cellular signaling via the transmembrane tyrosine kinase type 1 insulin-like growth factor receptor (IGF-I-R), which is also the receptor for IGF-I. Earlier studies with both cultured cells and transgenic mice, however, have suggested that in the embryo the insulin receptor (IR) may also be a receptor for IGF-II. In most cells and tissues, IR binds IGF-II with relatively low affinity. The IR is expressed in two isoforms (IR-A and IR-B) differing by 12 amino acids due to the alternative splicing of exon 11. In the present study we found that IR-A but not IR-B bound IGF-II with an affinity close to that of insulin. Moreover, IGF-II bound to IR-A with an affinity equal to that of IGF-II binding to the IGF-I-R. Activation of IR-A by insulin led primarily to metabolic effects, whereas activation of IR-A by IGF-II led primarily to mitogenic effects. These differences in the biological effects of IR-A when activated by either IGF-II or insulin were associated with differential recruitment and activation of intracellular substrates. IR-A was preferentially expressed in fetal cells such as fetal fibroblasts, muscle, liver and kidney and had a relatively increased proportion of isoform A. IR-A expression was also increased in several tumors including those of the breast and colon. These data indicate, therefore, that there are two receptors for IGF-II, both IGF-I-R and IR-A. Further, they suggest that interaction of IGF-II with IR-A may play a role both in fetal growth and cancer biology.

3T3 Cells↗
PubMed1999

Insulin and insulin-like growth factor-I (IGF-I) receptor overexpression in breast cancers leads to insulin/IGF-I hybrid receptor overexpression: evidence for a second mechanism of IGF-I signaling.

The insulin receptor (IR) form hybrids with the closely related insulin-like growth factor-I (IGF-I) receptor (IGF-I-R). Because most human breast carcinomas overexpress both the IR and the IGF-I-R, we evaluated whether the insulin/IGF-I hybrid receptor (Hybrid-R) is also overexpressed in these tumors and what role it plays in breast cancer biology. Using specific ELISAs and Western blots, we measured Hybrid-R content and function in 8 human cultured breast cancer cell lines and 39 human breast cancer specimens. Hybrid-R content and function were also compared to the content and function of the IR and the IGF-I-R. Hybrid-R content exceeded the IGF-I-R content in >75% of breast cancer specimens and was directly related to the molar ratio of both the IR and IGF-I-R content, suggesting that Hybrid-R formation occurred by random assembly of IR and IGF-I-R half-receptors. Hybrid-Rs became tyrosine autophosphorylated when breast cancer cells were exposed to IGF-I but not when they were exposed to insulin. In cells with an elevated Hybrid-R content, Hybrid-R autophosphorylation in response to IGF-I exceeded IGF-I-R autophosphorylation, suggesting that most of the IGF-I effect occurred via the Hybrid-R. Furthermore, Hybrid-Rs mediated growth in response to IGF-I, as indicated by experiments with blocking antibodies to the IGF-I-R. These data indicated therefore that: (a) Hybrid-Rs are present and play a major role in mediating the IGF-I signal in breast cancer; (b) their expression is directly related to IR overexpression; and (c) potential therapies designed to block IGF-I actions in breast cancer must take into account the role of these Hybrid-Rs.

Antibodies, Monoclonal↗
PubMed1998

Overexpression of the RON gene in human breast carcinoma.

Constitutive activation of the RON gene, known to code for the tyrosine-kinase receptor for Macrophage Stimulating Protein (also known as Scatter Factor 2), has been shown to induce invasive-metastatic phenotype in vitro. As yet, nothing is known about the expression of this novel member of the MET-oncogene family in spontaneously occurring human cancers. Here we report that Ron is expressed at abnormally high levels in about 50% primary breast carcinomas (35/74 patients). Among these, the expression is increased more than 20-fold in 12 cases and the overexpressed protein is constitutively phosphorylated on tyrosine residues. Notably, Ron is only barely detectable in epithelial cells of the mammary gland, and its expression remains unchanged in benign breast lesions (including adenomas and papillomas). Overexpression was observed in different histotypic variants of carcinomas; it is associated with the disease at any stage and correlates with the post-menopausal status. In breast carcinoma cells grown in vitro, activation of the Ron receptor resulted in proliferation, migration and invasion through reconstituted basement membranes. Altogether, these data suggest a role for the RON gene in progression of human breast carcinomas to the invasive-metastatic phenotype.

Animals↗